Remember hexacyclinol? Some readers are probably groaning and thinking “Oh, yes, indeed”, which may make up for the ones who are saying “Remember what?”
Hexacyclinol is a complex natural product, but after that statement the arguing begins. James La Clair published a synthesis of it in 2006 in Angewandte Chemie, one of the most prestigious chemistry journals, but the reception of the paper did nothing to help the prestige of either La Clair or the journal. Readers immediately seized on odd spectral data and experimental details to ask whether the molecule had been made at all and just how well the manuscript had been refereed.
The story got even messier later in the year when synthetic organic chemist Scott Rychnovsky weighed in with a paper suggesting that the structure of the natural product had been misassigned to start with. This was followed by a synthesis by John Porco and his group of his proposed structure, which turned out to match the NMR spectra of the original natural product. Since they also had an X-ray crystal structure, you would think that this would have ended the argument, at least at the level of what hexacyclinol looks like. The argument about what La Clair actually made, though, continued. And La Clair himself suggested that he and Rychnovsky had made two different molecules that just happened to have very similar NMR spectra.
Now a paper in Organic Letters is trying to clear that part of the story up, saying that ” indeed, the possibility that two molecules as complex as 1 and 2 may have indistinguishable NMR spectra carries an uneasy feel.” The authors, Giacomo Saielli and Allesandro Bagno from the University of Padova, return to the two proposed structures and calculate both their carbon and proton NMR spectra using what appear to be the best methods available for estimating their shifts and coupling constants.
The second structure fits much, much better, and the authors conclude that there is “hardly any doubt” that it’s the correct structure for hexacyclinol. In fact, they go further:
”The structure of hexacyclinol is confirmed to be 2. Furthermore, if 1 had been synthesized or was formed from an unforeseen reaction, its NMR spectra are sufficiently different from those of 2 as to guarantee their distinction.”
Note the “if it had been synthesized”. As far as I can tell, the remaining questions in this case aren't chemical. They're psychological. The original Ang. Chem. synthesis is certainly incapable of generating the real structure of hexacyclinol, but it also appears incapable of making the structure it claims to have made. Taken together with its original odd features, you have to wonder just what it was: a hoax? An odd and pointless work of fiction? Self-deception? We’ll probably never know. All we know is what it isn't.
For more reactions oto this latest news, see The Curious Wavefunction and The Chemistry Blog.